Composite materials made of collagen and glycosaminoglycan (GAG) have been shown to be highly useful for certain biochemical applications. For example, U.S. Pat. No. 4,060,081 (Yannas et al, 1977), the teachings of which are hereby incorporated by reference, discloses a multilayer membrane suitable for use as synthetic skin. The bottom layer, which is placed in contact with a woundbed, is a highly porous lattice comprising collagen that is crosslinked with GAG. This lattice provides a biophysical supporting structure in which cells can migrate and proliferate to heal the wound.
The typical procedures that have been used in the past to prepare collagen/GAG composite materials are described in U.S. application Ser. No. 30,183, filed on Apr. 16, 1979, now U.S. Pat. No. 4,280,954 and U.S. application Ser. No. 169,897, filed on July 17, 1980, now abandoned; the teachings of both of those applications are hereby incorporated by reference. Briefly, a preferred embodiment of those procedures comprises the following steps, in sequence:
1. Mechanically cutting and grinding a source of collagen into particulate form. PA1 2. Soaking the particulate collagen in dilute acetic acid. PA1 3. Homogenizing the solution in a blender. PA1 4. Adding a source of glycosaminoglycan which has been ground into particulate form. Typically, enough GAG is added to the solution to comprise about 6% to about 12% by dry weight of the composite material. The collagen/GAG mixture normally precipitates out of the acidic solution and forms a fibrous dispersion. PA1 5. The precipitate is homogenized in a blender. PA1 6. The solution is contacted with a crosslinking agent such as glutaraldehyde. PA1 7. The solution is quickly frozen in a shallow pan. PA1 8. The frozen dispersion is subjected to a high degree of vacuum, causing the acidic fluid to evaporate while the spatial configuration of the partially crosslinked fibrils is maintained.
The composite material thus formed may be treated by additional procedures to remove all traces of glutaraldehyde and to increase the crosslinking density and strength of the composite material.
The resulting collagen/GAG composite material exhibits some degree of incompatibility with the blood. For example, a small amount of platelet aggregation may occur over a period of several months if blood is in continuous contact with this material. This degree of blood incompatibility might be tolerable if the collagen/GAG composite material is to be biodegraded over a relatively short period of time, as is the case when it is used as artificial skin. However, that level of blood incompatibility can lead to certain problems in the use of collagen/GAG composite materials for prosthetic devices which are not rapidly biodegraded and which are in continuous contact with blood. For example, collagen/GAG material, in a less porous form than the lattice used for synthetic skin, may be useful for in-dwelling catheters, blood vessel replacement material, and other prosthetic devices. For such uses, it is advantageous to utilize a composite material that does not cause platelet aggregation to any detectable extent.